DESCRIPTION(Adapted from Applicant's Abstract): Chemotherapy for localized tumor treatment often is administered systemically, which delivers the chemotherapeutic agents throughout the body (as well as to the target sites), and can often cause unwanted side effects on other tissues in the body. An ideal scenario for localized delivery of therapeutic agents would be to sequester the drug in a package that would have minimal interaction with the body, and would contain the drug until release; then at the appropriate time and place in the body the drug could be released from the sequestering container. The main thrust of the proposed research is to combine the advantages of ultrasonic enhancement of drug transport and of micellar drug carrier into a novel technology which will deliver drugs predominantly to tissues exposed to localized acoustic energy. Ultrasound has many advantages as a mediator of drug delivery: the technique is non-invasive; it can be carefully controlled and focused on the target tissue; ultrasound appears to "activate," or to enhance the pharmacological activity of some drugs; it enhances drug transport through tissues and across cell membranes; and it can simultaneously create a hyperthermic condition which can enhance the destruction of cancerous tissues. Micellar drug carriers are advantageous because they encapsulate chemotherapeutic agents thus reducing the systemic concentration of the free drug and preventing unwanted drug interaction with healthy cells. The foundation of this proposal is our finding that ultrasound can enhance drug uptake by tumor cells when drug is delivered from micellar carriers. There are numerous potential advantages of the proposed technology over the state-of-the-art technologies: 1) long-circulating micelles will be used to encapsulate drug and reduce the systemic concentrations of free drug, thus reducing drug toxicity; 2) drug can be released in a controlled and localized volume by focusing acoustic energy on the volume; 3) the timing of drug release can be controlled; 4) the micelles will provide for the re-encapsulation of the drug outside of the localized target volume; 5) application of acoustic energy for enhancing drug uptake has additional benefit of hyperthermic therapy and acoustic potentialization of the drug; 6) ultrasound can penetrate to deep tissues, which most current techniques cannot provide.